Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer's disease.
Alzheimer Disease
/ genetics
Amyloid beta-Protein Precursor
/ genetics
Animals
Astrocytes
/ metabolism
Cell Proliferation
/ physiology
Disease Models, Animal
Disease Progression
Glial Fibrillary Acidic Protein
/ genetics
Inflammation
/ genetics
Memory, Short-Term
/ physiology
Mice
Mice, Transgenic
Spatial Memory
/ physiology
Aβ
astrocyte
glial fibrillary acidic protein (GFAP)
inflammation
synapses
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
21
05
2019
revised:
20
11
2019
accepted:
21
11
2019
pubmed:
5
12
2019
medline:
11
6
2021
entrez:
5
12
2019
Statut:
ppublish
Résumé
The role of astrocytes in the progression of Alzheimer's disease (AD) remains poorly understood. We assessed the consequences of ablating astrocytic proliferation in 9 months old double transgenic APP23/GFAP-TK mice. Treatment of these mice with the antiviral agent ganciclovir conditionally ablates proliferating reactive astrocytes. The loss of proliferating astrocytes resulted in significantly increased levels of monomeric amyloid-β (Aβ) in brain homogenates, associated with reduced enzymatic degradation and clearance mechanisms. In addition, our data revealed exacerbated memory deficits in mice lacking proliferating astrocytes concomitant with decreased levels of synaptic markers and higher expression of pro-inflammatory cytokines. Our data suggest that loss of reactive astrocytes in AD aggravates amyloid pathology and memory loss, possibly via disruption of amyloid clearance and enhanced neuroinflammation.
Identifiants
pubmed: 31799735
doi: 10.1002/glia.23759
pmc: PMC7383629
doi:
Substances chimiques
Amyloid beta-Protein Precursor
0
Glial Fibrillary Acidic Protein
0
glial fibrillary astrocytic protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1017-1030Subventions
Organisme : Medical Research Council
Pays : United Kingdom
Informations de copyright
© 2019 The Authors. Glia published by Wiley Periodicals, Inc.
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